Pungency of TRPV1 agonists is directly correlated with kinetics of receptor activation and lipophilicity.

TRPV1 (transient receptor potential vanilloid 1) is a ligand-gated ion channel expressed predominantly in nociceptive primary afferents that plays a key role in pain processing. In vivo activation of TRPV1 receptors by natural agonists like capsaicin is associated with a sharp and burning pain, frequently described as pungency. To elucidate the mechanisms underlying pungency we investigated a series of TRPV1 agonists that included both pungent and non-pungent compounds covering a large range of potencies.

TRP channels as emerging targets for pain therapeutics.

Background: The transient receptor potential (TRP) superfamily of ion channels are a large and diverse group that have received increased attention in recent years. The sub-family of thermo-TRPs which are regulated by temperature, among other physical and chemical stimuli, are of particular interest for the development of potential pain therapeutics.

Objective/methods: We review the advances in the field in recent years, focusing on a rationale for pain therapy and potential challenges associated with these targets.

Stable expression and characterisation of a human alpha 7 nicotinic subunit chimera: a tool for functional high-throughput screening.

A chimera comprising the N-terminal region of the human alpha7 nicotinic acetylcholine receptor, fused to the transmembrane/C-terminal domains of the mouse serotonin 5-HT3 receptor, was constructed. Injection of the chimera cDNA into Xenopus oocytes, or transient transfection in human embryonic kidney (HEK-293) cells, resulted in the expression of functional channels that were sensitive to nicotinic acetylcholine, but not serotonin receptor ligands. In both systems, the responses obtained from chimeric receptors inactivated more slowly than those recorded following activation of wild-type alpha7 receptors.